Overall manifestations and survival of pediatric patients with Langerhans cell histiocytosis. A middle-income country (mic) national multicenter study.

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of den-dritic cells. It is Mexico's ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018.

How long can the sperm wait? Effect of incubation time on ICSI outcomes.

In sperm processing for IVF/ICSI incubation times differ considerably both between and within assisted reproduction facilities. There is no established consensus on the optimal sperm incubation timings to maximize pregnancy rates, and the few studies addressing this association rely on manual and operator-dependent methods for time recording. The present retrospective cohort study includes 1169 ICSI cycles using fresh semen processed by swim-up.

Oxidative Stress in Reproduction: A Mitochondrial Perspective.

Mitochondria are fundamental organelles in eukaryotic cells that provide ATP through oxidative phosphorylation. During this process, reactive oxygen species (ROS) are produced, and an imbalance in their concentrations can induce oxidative stress (OS), causing cellular damage. However, mitochondria and ROS play also an important role in cellular homeostasis through a variety of other signaling pathways not related to metabolic rates, highlighting the physiological relevance of mitochondria-ROS interactions.

Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers.

Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control.

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique.

Background: Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care.

Objectives: To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART).

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B.

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control.

Gut Microbiota Linked to Sexual Preference and HIV Infection.

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects.

[Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes].

Case Report: A 58 year-old female was diagnosed with a juxtapapillary combined hamartoma of the retina and retinal pigment epithelium (CHR-RPE) in her left eye 14 years ago. Her visual acuity in that eye was 20/20. Recently, she came to our department with a sudden visual loss and metamorphopsis in her left eye.

HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.

Background: Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain.

RECall for automated genotypic tropism testing.

Standardization of sequence chromatogram analysis is required for consistent genotypic tropism determination across laboratories. A freely available, fast, and automated chromatogram analysis tool (RECall) provided tropism interpretations equivalent to those of manual sequence editing of 521 V3 loop HIV-1 population sequences, suggesting that RECall can be useful in standardizing genotypic tropism testing across laboratories.

Switching the third drug of antiretroviral therapy to maraviroc in aviraemic subjects: a pilot, prospective, randomized clinical trial.

Objectives: To evaluate the safety and efficacy of switching the third drug of antiretroviral treatment to maraviroc in aviraemic subjects infected with R5 HIV.

Patients And Methods: This is a pilot, prospective, randomized clinical trial (ClinicalTrials ID: NCT00966329). Eighty HIV-1-infected aviraemic adults on stable antiretroviral treatment for ≥1 year and no antiretroviral drug resistance were screened for the presence of non-R5 HIV by triplicate proviral V3 population sequencing.

Natural prevalence of HCV minority variants that are highly resistant to NS3/4A protease inhibitors.

Minority drug-resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre-existed in HCV infected patients.

Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice.

Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants.

A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy.

Background: The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain.

Methods: The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses.

Impact of CD4 T cell count on the outcome of planned treatment interruptions in early-treated human immunodeficiency virus-infected children.

Early highly active antiretroviral therapy is recommended in all vertically human immunodeficiency virus (HIV)-infected infants. We describe the long-term immunologic outcome after planned treatment interruption (PTI) in 7 children diagnosed and treated during acute HIV infection (age <12 weeks). Children had remained a median of 57 months off treatment, 3 of them indefinitely.

Mild improvement in mitochondrial function after a 3-year antiretroviral treatment interruption despite persistent impairment of mitochondrial DNA content.

Objective: The ability of a prolonged antiretroviral treatment interruption to reverse mitochondrial toxicity was evaluated in a sub-study of TIBET, a prospective trial examining antiretroviral treatment interruption guided by CD4+ cell count.

Patients And Methods: The study population was composed of patients from the TIBET study who had been followed for > or =96 weeks and whose peripheral blood mononuclear cells (PBMCs) had been collected at baseline and throughout the study period. Of the 201 patients included in the TIBET study, 38 were selected for the mitochondrial sub-study; 18 patients discontinued antiretroviral therapy for > or =96 weeks and 20 maintained therapy.

Variability in the plasma concentration of efavirenz and nevirapine is associated with genotypic resistance after treatment interruption.

Background: Selection and persistence of non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations during treatment interruptions (TIs) has been attributed to the long plasma half-life of these drugs. However, little is known about the contribution of variable NNRTI plasma levels before a TI. We evaluated the selection of NNRTI-related mutations and the coefficient of variation of NNRTI plasma concentrations during different TI periods.

The magnitude of interferon-gamma responses to human cytomegalovirus is predictive for HIV-1 disease progression.

Background: Human cytomegalovirus (HCMV) infection has been strongly associated to HIV-1 progression. We have investigated whether the magnitude of the overall peripheral blood mononuclear cell responses to HCMV stimulation correlated with HIV-1 progression.

Methods: Blood samples were collected from 75 HIV-1-positive individuals on highly active antiretroviral therapy with CD4 count>500 cells per cubic millimeter and undetectable HIV RNA just before interrupting treatment.

Secretion of interferon-gamma by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18.

The interferon (IFN)-gamma component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-gamma secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases.

Partial immunological and mitochondrial recovery after reducing didanosine doses in patients on didanosine and tenofovir-based regimens.

Background: Tenofovir disoproxil fumarate (TDF) has a safe toxicity profile; however, administration together with didanosine (ddl) increases ddl levels causing mitochondrial damage and CD4+ T-cell decline. We assessed whether a simple reduction of the ddl dose in patients receiving ddl (400 mg/day) and TDF could revert this side effect.

Methods: Immunological and mitochondrial changes were analysed in 20 patients at baseline, after 14 months of receiving ddl (400 mg/day), TDF (300 mg/day) and nevirapine (NVP; 400 mg/day) and 14 months after a ddl dose reduction to 250 mg/day.

Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions.

The role of antiretroviral history and genotypic resistance information as predictors of the first treatment interruption (TI) length in a CD4(+) cell count and plasma viremia-guided TI study (GTI) was assessed. Drug-resistance mutations (DRMs) were monitored in chronically HIV-1-infected subjects who underwent GTI. Patients were retrospectively classified into those who received monotherapy or dual therapy prior to HAART (pre-HAART group, n = 44) or directly initiated HAART (HAART group, n = 43).

Naive CD4(+) T cells and recent thymic emigrant levels in treated individuals with HIV: clinical relevance.

An increase in the levels of naive T cells after the administration of HAART is an indicator of the quality of immune reconstitution. We investigated whether levels of naive CD4 T cells (CD4(+)/CD45RA(+)) and of recent thymic emigrants (RTEs; CD4(+)/CD45RA(+)/CD31(+)) achieved in chronically treated HIV-infected patients could predict the length of time patients could interrupt antiretroviral treatment before their CD4 counts reached values < or =350 cells/mm(3) or HIV-1 RNA levels increased to > or =100,000 copies/ml (Tibet cohort). Serial measurements revealed that the level of naive CD4 T cells among patients was extremely variable (5-95%), but the values for each patient remained stable throughout the study.